These investigations represent the continuation of our studies on the Paneth cell in the small intestine and are designed to yield information on the secretory/endocytic function of these cells both in vivo and in vitro. Morphometric analysis of Paneth cells in the adult rat has provided baseline information for comparison to Paneth cells in neonatal and germfree animals, physiological states which represent radically altered states in the microbial flora of the gastrointestinal tract. The germfree animal model has been shown to possess diminished levels of immunoglobulin containing plasma cells and signs of increased numbers of Paneth cells. The effect of zinc-defficient diet in rats has been investigated, but has now shown any effect on the presence of lysozyme in Paneth cells nor has it caused any discernible change in the structural components of the Paneth cell. Using a combination of chelating agents, enzyme digestion, and mechanical shearing techniques an intestinal cell suspension rich in Paneth cells has been obtained which shows greater than 80% viability. These studies support a secretory/endocytic function for the Paneth cell in the immunological defense mechanisms associated with the gastrointestinal tract.